Neovascular PSMA expression is a common feature in malignant neoplasms of the thyroid

// Birthe Heitkotter 1, * , Konrad Steinestel 2, * , Marcel Trautmann 1 , Inga Grunewald 1 , Peter Barth 1 , Heidrun Gevensleben 3 , Martin Bogemann 4 , Eva Wardelmann 1 , Wolfgang Hartmann 1 , Kambiz Rahbar 5 and Sebastian Huss 1 1 Gerhard Domagk Institute of Pathology, University of Munster, Munster, Germany 2 Institute of Pathology, Military Hospital Ulm, Ulm, Germany 3 Institute of Pathology, Neuss, Germany 4 Department of Urology, University Hospital Munster, University of Munster, Munster, Germany 5 Department of Nuclear Medicine, University Hospital Munster, Munster, Germany * These authors contributed equally to this work Correspondence to: Sebastian Huss, email: sebastian.huss@ukmuenster.de Keywords: PSMA; thyroid cancer; tumor neoangiogenesis; prostate cancer Received: July 26, 2017      Accepted: November 15, 2017      Published: January 04, 2018 ABSTRACT Aim: PSMA (prostate-specific membrane antigen) is physiologically expressed in normal prostate tissue and over expressed in prostate cancer cells, therefore constituting a potential target for antibody-based radioligand therapy. Very recent imaging findings reported PSMA-PET/CT uptake in various thyroid lesions. We were therefore encouraged to systematically analyse PSMA expression in different benign and malignant thyroid lesions. Methods: Immunohistochemistry was used to detect PSMA expression in 101 thyroid lesions, while neovasculature was identified by CD34 immunostaining. Results: PSMA expression in the neovasculature was significantly more frequent in malignant tumors (36/63; 57.1%) compared to benign diseases (5/38; 13.2%; p = 0.0001). In addition, PSMA expression levels in the neovasculature of poorly and undifferentiated thyroid cancers were significantly higher compared to differentiated thyroid tumors ( p = 0.021). However, one case with a strong expression in follicular adenoma was identified. Conclusions: We conclude that neovascular PSMA expression is common in thyroid cancer but may also rarely be found in benign thyroid diseases, such as follicular adenoma. High expression in the tumor-associated neovasculature is predominantly found in poorly differentiated and undifferentiated (anaplastic) thyroid cancer. This knowledge is highly relevant when interpreting PSMA/PET-CT scans from patients with prostate cancer. In addition, our findings might provide a rationale for further evaluation of PSMA-targeted anti-neovascular or radioligand therapy in metastatic dedifferentiated thyroid cancer.